Auranofin

Auranofin is a gold salt classified by the World Health Organization as an antirheumatic agent. It has the brand name Ridaura.

Auranofin
Clinical data
Trade namesRidaura
AHFS/Drugs.comConsumer Drug Information
MedlinePlusa685038
Pregnancy
category
  • AU: B3
Routes of
administration		Oral
ATC code
Legal status
Legal status
  • AU: S4 (Prescription only)
  • UK: POM (Prescription only)
  • US: ℞-only
Pharmacokinetic data
Bioavailability40%[1][2]
Protein binding60%[1][2]
MetabolismPlasma membrane of the cell removes the acetyl groups of the glucose moiety.
Elimination half-life21-31 hours[1][2]
ExcretionUrine (60%), faeces[1][2]
Identifiers
IUPAC name
  • Gold(+1) cation; 3,4,5-triacetyloxy-6- (acetyloxymethyl) oxane-2-thiolate; triethylphosphanium
CAS Number
PubChem CID
DrugBank
ChemSpider
UNII
KEGG
ChEBI
ChEMBL
CompTox Dashboard (EPA)
ECHA InfoCard100.047.077
Chemical and physical data
FormulaC20H34AuO9PS0
Molar mass678.48 g·mol−1
3D model (JSmol)
SMILES
  • CCP(=[Au]S[C@H]1[C@@H]([C@H]([C@@H]([C@H](O1)COC(=O)C)OC(=O)C)OC(=O)C)OC(=O)C)(CC)CC
InChI
  • InChI=1S/C14H20O9S.C6H15P.Au/c1-6(15)19-5-10-11(20-7(2)16)12(21-8(3)17)13(14(24)23-10)22-9(4)18;1-4-7(5-2)6-3;/h10-14,24H,5H2,1-4H3;4-6H2,1-3H3;/q;;+1/p-1/t10-,11-,12+,13-,14+;;/m1../s1 Y
  • Key:AUJRCFUBUPVWSZ-XTZHGVARSA-M Y
 NY (what is this?)  (verify)

Use

Auranofin is used to treat rheumatoid arthritis. It improves arthritis symptoms including painful or tender and swollen joints and morning stiffness.[3] Auranofin is a safer treatment compared to the more common injectable gold thiolates (gold sodium thiomalate and gold thioglucose), but meta-analysis of 66 clinical trials concluded that it is somewhat less effective.[4]

The drug was approved for the treatment of rheumatoid arthritis in 1985. No longer a first-line treatment for rheumatoid arthritis, due to its adverse effects, "most of which are associated with long-term use for chronic disease. The most common adverse effects are gastrointestinal complaints such as loose stools, abdominal cramping and watery diarrhea, which can develop in the early months of treatment. The development of loose stools occurs in 40 % of patients, while watery diarrhea is reported in just 2–5 % of patients, and in most cases these symptoms were alleviated by reducing or splitting the dose".[5]

Research

HIV infection

Auranofin is under investigation as a means of reducing the viral reservoir of HIV that lies latent in the body's T-cells despite treatment with antiretroviral therapy.[6] The drug was shown to reduce the amount of latent virus in monkey trials.[7] A human study testing auranofin and other investigational treatments is ongoing in Brazil.[8] Preliminary results show that auranofin contributed to a decrease in the viral reservoir.[9]

Amebiasis

Auranofin has been identified in a high-throughput drug screen as 10 times more potent than metronidazole against Entamoeba histolytica, the protozoan agent of human amebiasis. Assays of thioredoxin reductase and transcriptional profiling suggest that the effect of auranofin on the enzyme enhances the sensitivity of the trophozoites to reactive oxygen-mediated killing in mouse and hamster models; the results are marked reductions of the number of parasites, the inflammatory reaction to the infestation, and the damage to the liver.[10][11][12]

Acanthamoeba Keratitis and Primary Amoebic Meningoencephalitis

Auranofin may be useful in the prevention and control of Acanthamoeba infections, and in the treatment of primary amoebic meningoencephalitis, caused by pathogenic free-living amoebae Acanthamoeba spp. and Naegleria fowleri, respectively.[13][14]

Tuberculosis

In a cell-based screen, auranofin showed potent activity against replicating and non-replicating M. tuberculosis as well as other gram-positive bacteria. Auranofin protected mice from an otherwise lethal infection with methicillin-resistant S. aureus (MRSA). The drug acts in a similar manner in bacteria as in parasites by inhibiting thioredoxin reductase (TrxR). Studies in humans are needed to evaluate the potential of this drug to treat Gram-positive bacterial infections in humans.[15]

Ovarian cancer

Drug-screening reveals auranofin induces apoptosis in ovarian cancer cells in vitro.[16][17]

COVID-19

Auranofin may inhibit replication of SARS-CoV-2, the virus responsible for causing COVID-19 in cell culture. Inflammation may also be reduced.[18]

Etymology

The brand name Ridaura was coined from the phrase Remission-Inducing Drug + Auranofin. [19]

References
  1. Kean WF, Hart L, Buchanan WW (May 1997). "Auranofin". British Journal of Rheumatology. 36 (5): 560–72. doi:10.1093/rheumatology/36.5.560. PMID 9189058.
  2. "Ridaura (auranofin) dosing, indications, interactions, adverse effects, and more". Medscape Reference. WebMD. Retrieved 13 March 2014.
  3. MedlinePlus DrugInfo medmaster-a685038
  4. Felson DT, Anderson JJ, Meenan RF (October 1990). "The comparative efficacy and toxicity of second-line drugs in rheumatoid arthritis. Results of two metaanalyses". Arthritis and Rheumatism. 33 (10): 1449–61. doi:10.1002/art.1780331001. PMID 1977391.
  5. Roder C, Thomson MJ (March 2015). "Auranofin: repurposing an old drug for a golden new age". Drugs in R&D. 15 (1): 13–20. doi:10.1007/s40268-015-0083-y. PMC 4359176. PMID 25698589.
  6. Gold-based drug shows promise in clearing HIV reservoir in monkey study. Keith Alcorn. AIDSmaps.com. Accessed 23 April 2011.
  7. Lewis MG, DaFonseca S, Chomont N, Palamara AT, Tardugno M, Mai A, et al. (July 2011). "Gold drug auranofin restricts the viral reservoir in the monkey AIDS model and induces containment of viral load following ART suspension". AIDS. 25 (11): 1347–56. doi:10.1097/QAD.0b013e328347bd77. PMID 21505294. S2CID 19698337.
  8. "Multi Interventional Study Exploring HIV-1 Residual Replication: a Step Towards HIV-1 Eradication and Sterilizing Cure - Full Text View - ClinicalTrials.gov". Retrieved 2018-08-14.
  9. "Auranofin plus nicotinamide impact HIV reservoir among ART suppressed HIV individuals". Retrieved 2018-08-16.
  10. Debnath A, Parsonage D, Andrade RM, He C, Cobo ER, Hirata K, et al. (June 2012). "A high-throughput drug screen for Entamoeba histolytica identifies a new lead and target". Nature Medicine. 18 (6): 956–60. doi:10.1038/nm.2758. PMC 3411919. PMID 22610278.
  11. "Drug Found for Parasite That Is Major Cause of Death Worldwide". Science Daily.
  12. "Arthritis Drug Effective Against Global Parasite, Study Suggests". Science Daily.
  13. Loufouma Mbouaka A, Leitsch D, Koehsler M, Walochnik J (August 2021). "Antimicrobial effect of auranofin against Acanthamoeba spp". International Journal of Antimicrobial Agents. 58 (5): 106425. doi:10.1016/j.ijantimicag.2021.106425. PMID 34419578. S2CID 237267846.
  14. Peroutka-Bigus N, Bellaire BH (July 2019). "Antiparasitic Activity of Auranofin against Pathogenic Naegleria fowleri". The Journal of Eukaryotic Microbiology. 66 (4): 684–688. doi:10.1111/jeu.12706. PMID 30520183. S2CID 54468504.
  15. Harbut MB, Vilchèze C, Luo X, Hensler ME, Guo H, Yang B, et al. (April 2015). "Auranofin exerts broad-spectrum bactericidal activities by targeting thiol-redox homeostasis". Proceedings of the National Academy of Sciences of the United States of America. 112 (14): 4453–8. Bibcode:2015PNAS..112.4453H. doi:10.1073/pnas.1504022112. PMC 4394260. PMID 25831516.
  16. Park SH, Lee JH, Berek JS, Hu MC (October 2014). "Auranofin displays anticancer activity against ovarian cancer cells through FOXO3 activation independent of p53". International Journal of Oncology. 45 (4): 1691–8. doi:10.3892/ijo.2014.2579. PMC 4151813. PMID 25096914.
  17. Oommen D, Yiannakis D, Jha AN (2016). "BRCA1 deficiency increases the sensitivity of ovarian cancer cells to auranofin". Mutation Research. 784–785: 8–15. doi:10.1016/j.mrfmmm.2015.11.002. PMID 26731315.
  18. "Georgia State Researchers Find Rheumatoid Arthritis Drug Is Effective Against Coronavirus". News Hub. 15 April 2020. Retrieved 15 April 2020.
  19. Lévy, Joseph Josy; Garnier, Catherine (2007). La chaîne des médicaments: Perspectives pluridisciplinaires [The Drug Supply Chain: A Multidisciplinary Perspective] (in French). PUQ Presse de l'Université du Québec. ISBN 978-2760519510 – via Google Books.

Further reading
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